Faculty Bibliography

BACKGROUND: Myasthenia gravis (MG) and neuromyelitis optica (NMO, also known as Devic disease) are rare autoimmune disorders, with upper-limit prevalence estimates in the general population of 15 per 100,000 and 5 per 100,000, respectively. To our knowledge, an association between these diseases has not been previously reported. OBJECTIVES: To describe 4 patients with MG who developed NMO after thymectomy and to analyze possible causes of apparent increased prevalence of NMO among patients with MG. DESIGN: Case series. PATIENTS: Four patients with MG who underwent thymectomy. INTERVENTIONS: None. RESULTS: The prevalence of MG within the published cohort of patients with NMO is more than 150 times higher than that in the general population. CONCLUSION: Dysregulation of B-cell autoimmunity in myasthenia, possibly exacerbated by loss of control over autoreactive cells as a result of thymectomy, may predispose patients to the development of NMO

In response to endotoxemia induced by administration of lipopolysaccharide, a complex series of reactions occurs in mammalian tissues. During this inflammation response, cells produce different mediators, such as reactive oxygen species, a number of arachidonic acid metabolites, and cytokines. The reactive oxygen species thus generated have been suggested to produce tissue injury as a result of macromolecular damage or by interfering with regulatory processes. They may also act as important signaling molecules to induce redox-sensitive genes. We report here that transgenic mice overexpressing 2 major forms of human glutathione peroxidases (GPs), intra- and extracellular GP, are able to modulate host response during endotoxemic conditions. We show that these animals have a decreased hypotension and increased survival rate after administration of a high dosage of lipopolysaccharide. Overexpression of GPs alters vascular permeability and production of cytokines (interleukin-1 beta and tumor necrosis factor-alpha) and NO, affects arachidonic acid metabolism, and inhibits leukocyte migration. These results suggest an important role for peroxides in pathogenesis during endotoxemia, and GPs, by regulating their level, may prove to be good candidates for antioxidant therapy to protect against such injury